Field of the Invention
The present invention relates to a method for producing an aqueous suspension of precious metal nanoparticles with reliable particle size control.
Description of the Related Art
Precious metal nanoparticles (PMNPs) and colloidal PMNPs, also called precious metal nanocolloids (PMNCs), are being widely investigated for their potential use in a wide variety of biological and medical applications. The precious metals (PM) of interest include gold, silver, copper, platinum, palladium, rhodium, ruthenium, iridium, osmium and any alloys including at least one of these metals. Applications of the PMNCs include using the PMNC as an imaging agent, a sensing agent, a gene-regulating agent, a targeted drug delivery carrier, or as a photoresponsive antibacterial therapeutic agent. Most of these applications require a surface modification on the PMNPs, which is also referred to as a surface functionalization.
Another important application of PMNPs is the field of spectroscopy by utilizing the unique optical properties originating from the localized surface plasmon resonance due to the collective motion of free electrons in the nanoparticles. Surface enhanced Raman scattering or surface enhanced Raman spectroscopy (SERS) is a very sensitive and valuable analytical method of spectroscopy that enhances Ramen scattering by molecules adsorbed onto or located on certain metal surfaces. The signal enhancement can be as high as 106 or higher, thus the method can be used to detect single molecules or analytes of interest. The exact mechanism of the enhancement is not currently known, but typical surfaces for SERS comprise particles or roughened surfaces of precious metals such as silver, gold, copper, palladium, or platinum.
For these applications, PMNPs having an average diameter size of about 10 nm or larger are advantageous with respect to the following three features. First, PMNPs having a size of about 10 nm or larger give a larger signal enhancement when used for plasmonic spectroscopy such as SERS. For example, in the case of gold nanoparticles, 46-74 nm size in diameter is reported to be optimum for SERS according to “SERS enhancement by aggregated Au colloids: effect of particle size”, Phys. Chem. Chem. Phys., 11, 7455 (2009) by Steven E. J. Bel et al. In the case of silver nanoparticles the optimum size is about 50 to 60 nm in diameter according to “Optimal Size of Silver Nanoparticles for Surface-Enhanced Raman Spectroscopy”, J. Phys. Chem. C 115, 1403 (2011) by K. G. Stamplecoskie et al.
Second, PMNPs having a size of about 10 nm or larger are sufficiently large enough that one can use centrifugal techniques to purify or isolate different sized populations of them during their use or during functionalization reactions with ligands. Generally, surface functionalization of these nanoparticles with ligand molecules is done by adding the ligand molecules to the colloidal solution in an excess amount, meaning more than the amount required for these molecules to occupy the entire available surface of the nanoparticles. Then centrifugal purification may be applied to remove the unattached molecules from the colloidal solution. However, the inventors found it difficult to induce centrifugal sedimentation of the PMNPs when the size of PMNPs becomes smaller than 10 nm, even in case of gold, which has one of the largest relative densities of the precious metals.
Third, a larger particle has a larger surface area, making it capable of having a variety of functional molecules loaded per particle. For example, the functional molecules may be different fluorescent molecules for different fluorescent wavelengths or they may be Raman active molecules having different vibration spectrum.
Currently, the majority of the PMNCs are being made by bottom-up fabrication methods like chemical synthesis methods such as those based on a reduction of the precious metal in an ionic state or those based on forming complex ions with ligand molecules. However, bottom-up fabrication methods have great difficulty in making larger particles in a controlled manner because of the difficulty of controlling the particle growth in these methods. Also, chemical synthesis inherently produces chemical by-products as a result of the counterpart reaction during the reduction of the precious metals resulting in residual ions in an electrolyte of the colloidal solution. Furthermore, currently commercially-available PMNCs made by chemical synthesis contain stabilizing agents that prevent the PMNPs from aggregating and precipitating out of the colloidal solution. The presence of the stabilizing agents or residual ions of the chemical by-products could result in undesirable noise signals which impair the sensitive spectroscopic measurements such as SERS.
Pulsed laser ablation in liquid (PLAL) is a method for synthesizing PMNPs directly from bulk materials, and can provide totally ligand-free PMNPs that are stable in a colloidal liquid that does not contain any stabilizers. Commonly owned U.S. Patent Application Pub. No. 2012/0225021, filed on Mar. 2, 2011 and assigned Ser. No. 13/038,788 discloses a method of producing stable bare colloidal gold nanoparticles in water by a top-down fabrication method using a PLAL method, with bulk gold as a target material.
Notwithstanding such recent advancements in PLAL methods, accurate and reliable size control of the PMNPs for PLAL is still a challenge.
For example, challenges associated with nanoparticle size control were recently demonstrated by C. Rehbock et al. (Phys. Chem. Chem. Phys., “Size control of laser-fabricated surfactant-free gold nanoparticles with highly diluted electrolytes and their subsequent bio-conjugation”, published on 3 Oct. 2012, DOI:10.1039/C2CP42641B. In this article a method was shown of generating gold nanoparticles (AuNPs) and subsequently bio-conjugated them by using a nanosecond PLAL approach and size control with a highly diluted electrolyte. More specifically, the AuNPs were generated and dispersed into a carrier steam of water containing a trace amount of salts. To control the size of the AuNPs by PLAL with the highly diluted electrolyte, C. Rehbock et al. demonstrated size control of the AuNPs by introducing a known amount of specific ions into the carrier stream of water. To produce the AuNPs' in a diameter of 10 nm or larger requires a precise control of ion concentration, as shown in C. Rehbock et al., because the produced size of AuNPs changes strongly depending on the ion concentration when the ion concentration is in a range below 30 micromole (μM). In this low concentration range the effect of a trace amount of externally introduced ions, such as a contamination, on nanoparticle size are no longer negligible. Such a trace amount of externally introduced ions can come not only from a contamination, but also from ions leaching from a water container into the water used for PLAL. Also, the uncertainty of the amount of externally introduced ions includes those coming from dissolved gases such as from the atmosphere the water has been exposed to before or during PLAL In principle, there are various ways to analyze individual ions in the electrolyte based on an element analysis such as inductively coupled plasma mass spectroscopy (ICP-MS), or based on molecular analyses such as high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), Fourier transform infrared spectroscopy (FTIR) and Raman scattering (RS). However, all these measurements are too costly and time consuming to perform every time before a PLAL to quantify the net ion concentration, which actually determines the size of produced PMNPs in the PLAL process.